title: The inhibition of cocaine-induced locomotor activity by CART 55-102 is lost after repeated cocaine administration.
abstract: CART peptide is known for having an inhibitory effect on cocaine- and dopamine-mediated actions after acute administration of cocaine and dopamine. In this regard, it is postulated to be a homeostatic, regulatory factor on dopaminergic activity in the nucleus accumbens (NAc). However, there is no data on the effect of CART peptide after chronic administration of cocaine, and this study addresses this. It was found that CART peptide blunted cocaine-induced locomotion (LMA) after acute administration of cocaine, as expected, but it did not affect cocaine-mediated LMA after chronic administration of cocaine. The loss of CART peptide's inhibitory effect did not return for up to 9 weeks after stopping the repeated cocaine administration. It may not be surprising that homeostatic regulatory mechanisms in the NAc are lost after repeated cocaine administration, and that this may be a mechanism in the development of addiction.
authors.affiliation: Yerkes National Primate Research Center of Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA. mjob@emory.edu
authors.forename: Martin O
authors.initials: MO
authors.lastname: Job
authors.forename: Li L
authors.initials: LL
authors.lastname: Shen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kuhar
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D003042:Cocaine; D018765:Dopamine Uptake Inhibitors; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C428723:cocaine- and amphetamine-regulated transcript protein (55-102); D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
keywords: Acute; CART 55-102; CART peptide; Chronic; Cocaine